a cross-species analysis of a mouse model of breast cancer-specific osteolysis and human bone metastases using gene expression profiling小鼠模型的跨物种分析乳腺癌骨转移特异的骨质溶解和人类使用基因表达分析.pdfVIP

Sadanandam et al. BMC Cancer 2011, 11:304 /1471-2407/11/304 RESEARCH ARTICLE Open Access A Cross-Species Analysis of a Mouse Model of Breast Cancer-Specific Osteolysis and Human Bone Metastases Using Gene Expression Profiling 1,6* 2 3,4 5 1* Anguraj Sadanandam , Mitsuru Futakuchi , Costas A Lyssiotis , William J Gibb and Rakesh K Singh Abstract Background: Breast cancer is the second leading cause of cancer-related death in women in the United States. During the advanced stages of disease, many breast cancer patients suffer from bone metastasis. These metastases are predominantly osteolytic and develop when tumor cells interact with bone. In vivo models that mimic the breast cancer-specific osteolytic bone microenvironment are limited. Previously, we developed a mouse model of tumor-bone interaction in which three mouse breast cancer cell lines were implanted onto the calvaria. Analysis of tumors from this model revealed that they exhibited strong bone resorption, induction of osteoclasts and intracranial penetration at the tumor bone (TB)-interface. Methods: In this study, we identified and used a TB microenvironment-specific gene expression signature from this model to extend our understanding of the metastatic bone microenvironment in human disease and to predict potential therapeutic targets. Results: We identified a TB signature consisting of 934 genes that were commonly (among our 3 cell lines) and specifically (as compared to tumor-alone area within the bone microenvironment) up- and down-regulated 2-fold at the TB interface in our mouse osteolytic model. By comparing the TB signature with gene expression profiles from human breast metastases and an in vitro osteoclast mode